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EP0620750B1 - Dispositif de remplacement de fil de guidage - Google Patents

Dispositif de remplacement de fil de guidage Download PDF

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Publication number
EP0620750B1
EP0620750B1 EP93904480A EP93904480A EP0620750B1 EP 0620750 B1 EP0620750 B1 EP 0620750B1 EP 93904480 A EP93904480 A EP 93904480A EP 93904480 A EP93904480 A EP 93904480A EP 0620750 B1 EP0620750 B1 EP 0620750B1
Authority
EP
European Patent Office
Prior art keywords
guidewire
distal
proximal
shaft section
catheter
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP93904480A
Other languages
German (de)
English (en)
Other versions
EP0620750A1 (fr
EP0620750A4 (fr
Inventor
Motasim M. Sirhan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott Cardiovascular Systems Inc
Original Assignee
Advanced Cardiovascular Systems Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Advanced Cardiovascular Systems Inc filed Critical Advanced Cardiovascular Systems Inc
Publication of EP0620750A1 publication Critical patent/EP0620750A1/fr
Publication of EP0620750A4 publication Critical patent/EP0620750A4/fr
Application granted granted Critical
Publication of EP0620750B1 publication Critical patent/EP0620750B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
    • A61M25/0172—Exchanging a guidewire while keeping the catheter in place
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/104—Balloon catheters used for angioplasty
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0043—Catheters; Hollow probes characterised by structural features
    • A61M2025/0063—Catheters; Hollow probes characterised by structural features having means, e.g. stylets, mandrils, rods or wires to reinforce or adjust temporarily the stiffness, column strength or pushability of catheters which are already inserted into the human body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
    • A61M2025/0183—Rapid exchange or monorail catheters

Definitions

  • This invention generally relates to intravascular procedures, such as percutaneous transluminal coronary angioplasty (PTCA), and particularly to the exchange of guidewires during such procedures.
  • PTCA percutaneous transluminal coronary angioplasty
  • a guiding catheter having a preshaped distal tip is percutaneously introduced into the cardiovascular system of a patient and advanced therein until the preshaped distal tip thereof is disposed within the aorta adjacent the ostium of the desired coronary artery.
  • the guiding catheter is twisted or torqued from its proximal end, which extends outside of the patient, to turn the distal tip of the guiding catheter so that it can be guided into the coronary ostium and seated therein.
  • a dilatation catheter having a dilatation balloon on the distal end thereof and a guidewire slidably disposed within an inner lumen of the dilatation catheter are introduced into and advanced through the proximal end of the guiding catheter to the distal tip of the guiding catheter seated within the coronary ostium.
  • the distal tip of the guidewire is usually manually shaped (curved) by the physician or one of the attendants before it is introduced into the guiding catheter along with the dilatation catheter.
  • the shaped distal tip of the guidewire is first advanced out the distal tip of the guiding catheter into the patient's coronary artery.
  • a torque is applied to the proximal end of the guidewire, which extends out of the proximal end of the guiding catheter as it is advanced within the coronary anatomy, to guide the curved or otherwise shaped distal end of the guidewire into a branch artery targeted for dilatation.
  • the advancement of the guidewire within the target artery continues until it crosses the lesion to be dilated.
  • the dilatation catheter is then advanced out of the distal tip of the guiding catheter, over the previously advanced guidewire, until the balloon on the distal extremity of the dilatation catheter is properly positioned across the lesion to be dilated.
  • the flexible, relatively inelastic dilatation balloon on the catheter is inflated to a predetermined size with radiopaque liquid at relatively high pressures (e . g ., generally 4-12 atmospheres) to dilate the stenosed region of the diseased artery.
  • One or more inflations of the balloon may be required to complete the dilatation of the stenosis.
  • the balloon is deflated so that the dilatation catheter can be removed from the dilated stenosis and so that blood flow can resume through the dilated artery.
  • Patent 4,638,805 (Powell); U.S. Patent 4,748,986 (Morrison et al .); U.S. Patent 4,898,577 (Badger et al .); U.S. Patent 4,748,982 (Horzewski et al .); and U.S. Patent 4,821,722 (Miller et al.).
  • US Patent 4,988,356 discloses a system for facilitating exchange of catheters in the body of a patient, and for transporting such catheters to selected sites within the patient.
  • This dilatation catheter has a short guidewire receiving sleeve or inner lumen extending through the distal portion of the catheter.
  • the sleeve extends proximally a distance of at least 10 cm and usually not more than about 50 cm from a first guidewire port in the distal end of the catheter to a second guidewire port in the catheter spaced proximally from the inflatable balloon of the catheter.
  • a slit is preferably provided in the catheter wall which extends distally from the second guidewire port, preferably to a location proximal to the proximal end of the inflatable balloon to aid in the removal of the catheter from a guidewire.
  • the in-place guidewire may need to be replaced with another guidewire having a different structure, e.g. from a floppy-type design with a separate shaping ribbon to an intermediate or standard with a core wire which extends to the distal tip of the guidewire, or it may need to be withdrawn in order to reshape the distal tip and then be reinserted.
  • the guidewire is referred to herein as the replacement guidewire.
  • This invention is directed to an intravascular guidewire exchange device which provides for the exchange of the guidewire, particularly with in the coronary arteries of a human patient during an angioplasty procedure.
  • the present invention provides an intravascular guidewire exchange device, comprising an elongated shaft, said shaft including proximal and distal shaft sections and the distal end of said distal shaft section is adapted for projection into a guidewire port of a catheter, characterized in that: the distal shaft section comprises an outer sleeve at the junction with the proximal shaft section and has at least a distal portion thereof configured to be advanced through the patient's coronary artery and into a proximal guidewire port of a rapid exchange type intravascular catheter, a first guidewire port in the distal end of said distal shaft section, a second guidewire port in the proximal end of said distal shaft section, and a first open guidewire receiving inner lumen which is disposed within said distal shaft section and extending form the first guidewire port in the distal end thereof to the second guidewire port; and said proximal shaft section having a length greater than said distal shaft section and the distal end of the proximal shaft section being secured to the distal shaft section
  • the guidewire exchange device of the invention generally comprises an elongated catheter shaft with a guidewire receiving inner lumen extending therein to a guidewire port in the distal end of the catheter.
  • a proximal guidewire port is provided in the catheter shaft spaced longitudinally at least 1 cm or more from the distal end of the shaft which is in fluid communication with the guidewire receiving inner lumen.
  • the catheter shaft includes a relatively long proximal tubular section and a relatively short distal tubular section.
  • the proximal guidewire port is located at or near the transition between the proximal and distal tubular sections of the exchange device.
  • the distal tubular section is preferably adapted to guide the proximal end of a guidewire out the proximal guidewire port as the proximal end of the guidewire is advanced through the inner lumen of the guidewire exchange device from the distal guidewire port.
  • the transition between the proximal and distal sections are slightly angled, e.g. about 5 to about 40 degrees, preferably about 5 to about 30 degrees, so that the proximal end of the guidewire will advance out the proximal guidewire port.
  • the distal end of the distal tubular section of the guidewire exchange device is shaped, e . g . tapered, and dimensioned so as to be easily inserted into the proximal guidewire port of a readily exchangeable catheter as the exchange device is advanced over a guidewire which extends out the proximal guidewire port of the readily exchangeable catheter.
  • the guidewire exchange device is adapted to be advanced over a guidewire, which is disposed within a patient, either until the distal tip of the exchange device is seated within the proximal guidewire port of the readily exchangeable catheter or the distal end of the exchange device has been advanced through the guidewire port and well within the short guidewire receiving inner lumen which extends within the distal portion of the readily exchangeable catheter.
  • the in-place guidewire can then be withdrawn proximally from the catheter and the patient's arterial system by pulling on the proximal end of the guidewire which extends out of the patient.
  • a replacement guidewire may then be advanced through the inner lumen of the exchange device, through the proximal guidewire port in the dilatation catheter and through the inner lumen of the catheter until the guidewire extends out the distal guidewire port in the dilatation catheter.
  • the distal portion of the distal tubular member of the exchange device is adapted to be inserted into and be advanced through essentially the entire length of the relatively short guidewire receiving inner lumen of the readily exchangeable catheter is particularly suitable for use with a rapid exchange type dilatation catheters having perfusion ports, as described in the previously discussed McInnes et al . applications, which allow blood to pass through the guidewire receiving inner lumen.
  • a rapid exchange type dilatation catheters with perfusion holes in the catheter shaft
  • advancement of a replacement guidewire within the guidewire receiving inner lumen sometimes results in the passage of the guidewire out one of the perfusion holes in the catheter wall rather than the guidewire port in the distal end of the catheter.
  • the distal extremity of the guidewire exchange device of the invention is positioned within the guidewire receiving inner lumen of the readily exchangeable catheter, the replacement guidewire is directed to the distal guidewire port and cannot be advanced out one of the perfusion holes.
  • junction between the distal and proximal sections can be used in a variety of intraluminal and intravascular devices including readily exchangeable dilatation catheters such as described in the aforementioned Yock and Horzewski et al. patents.
  • FIG. 1 is an elevational view of the exchange device of the invention.
  • FIG. 2 is an enlarged elevational view in longitudinal section of the junction between the distal and proximal tubular members of the exchange device taken along the lines 2-2 shown in FIG. 1.
  • FIG. 3 is a transverse cross-sectional view taken along the lines 3-3 shown in FIG. 1.
  • FIG. 4 is a transverse cross-sectional view taken along the lines 4-4 shown in FIG. 1.
  • FIG. 5. is an elevational view of a guiding catheter and a readily exchangeable dilatation catheter with a guidewire exchange device having features of the invention.
  • FIG. 6 is an enlarged view of the section of the assembly shown in FIG. 5 which is encircled by the ellipse 6.
  • FIGS. 7-14 illustrate the exchange of a guidewire utilizing the exchange device shown in FIGS. 1-4.
  • FIG. 15 is an enlarged longitudinal cross-sectional view similar to FIG. 6 of an alternate embodiment of the invention used with a dilatation catheter which has the capability of perfusing blood distal to the catheter upon the inflation of the balloon.
  • FIGS. 1-4 depict a guidewire exchange device 10 embodying features of the invention.
  • the exchange device 10 includes a relatively long proximal tubular section 11, a relatively short distal tubular section 12 and an outer sleeve 13 bonded at the junction between the proximal and distal tubular sections to the ends thereof.
  • the larger proximal end of the outer sleeve 13 defines a proximal guidewire port 14 communicating with the portion of the guidewire-receiving inner lumen 15 which extends within the distal tubular section 12 through a passageway 16.
  • the distal tip 17 of the exchange device 10 may be beveled or tapered as shown to facilitate the entry thereof into the proximal guidewire port of a readily exchangeable catheter.
  • the proximal tubular section 11 is relatively stiff in comparison to the distal tubular section 12 to provide a high degree of pushability to the catheter.
  • the proximal tubular section is formed of hypotubing 18 and a coating or jacket 19 of plastic material which is secured to the exterior of the hypotubing.
  • the hypotubing is provided with a slit 20 having a width in excess of the maximum transverse dimension of the replacement guidewire 21 (shown in phantom) to be used and the jacket with a slit 22 having a much smaller spacing. This allows the replacement guidewire 21 to be stripped from the inner lumen 25 of the proximal section 11 after it has been advanced into the distal section 12.
  • a Luer adapter 24 is mounted to the proximal end of the proximal tubular section 11 and is either removable or is provided a slit continuous with slits 20 and 22 to facilitate removal of the replacement guidewire 21 from the inner lumen 25 in the proximal tubular section 11.
  • Fig. 4 illustrates a transverse cross-sectional view of the distal tubular section 12 which is a relative flexible section formed of suitable plastic material.
  • FIG. 5 depicts a dilatation catheter assembly which includes a guiding catheter 26, a readily exchangeable dilatation catheter 27, an in-place guidewire 28, a replacement guidewire 21 and the guidewire exchange device 10.
  • an adapter (not shown) would be provided on the proximal end of the guiding catheter which has a hemostatic valve large enough to accommodate the guidewire, the dilatation catheter and the exchange device.
  • the area enclosed by the ellipse 6 shown in FIG. 5 is depicted in an enlarged cross-sectional view in FIG. 6.
  • the distal tip of the exchange device 10 is shown seated within the proximal guidewire port 29 of the dilatation catheter 27.
  • a first guidewire 28 is in-place within the guidewire receiving inner lumen 30 of the dilatation catheter 27 and extends through the inner lumen 15 of the guidewire exchange device 10, the passageway 16 and the proximal port 14.
  • the sleeve 13 is preferably enlarged at its proximal extremity and slightly angled as shown, e.g.
  • a second or replacement guidewire 21 is shown in phantom disposed within the inner lumen 25 within the proximal tubular section 11.
  • FIGS. 7-14 The exchange of an in-place guidewire 28 with a replacement guidewire 21 is illustrated in the sequence of FIGS. 7-14.
  • the in-place guidewire is disposed within the short guidewire receiving inner lumen 30 (not shown) in the distal section of the readily exchangeable dilatation catheter 27.
  • Both the in-place guidewire 28 and the dilatation catheter 27 are disposed within a guiding catheter 26, as shown in FIG. 5 with the distal end of the dilatation catheter extending out the distal end of the guiding catheter.
  • the distal end of the guiding catheter 26 is seated within the ostium of the patient's coronary artery during the angioplasty procedure so as to guide the guidewires and dilatation catheters into the patient's coronary anatomy.
  • the proximal end of the in-place guidewire is inserted, i.e. back-loaded, into the distal port of the guidewire exchange device 10 and through the inner lumen 15 and passageway 16 until the proximal end exits the proximal port 14 at the junction between the proximal and distal tubular sections 11 and 12.
  • the proximal end of the guidewire may then be manually grasped and the exchange device 10 advanced, as shown in FIG. 8, over the in-place guidewire 28 until the distal tip of the exchange device is seated within the proximal guidewire port 29 in the readily exchangeable dilatation 27, as shown in FIG. 9.
  • the in-place guidewire 28 may be withdrawn from the dilatation catheter 27 and the patient as shown by the arrow in FIG. 10.
  • a replacement guidewire 21 is advanced through the adapter 24 as shown in FIG. 11 and the inner lumens 15 and 25 of the exchange device 10 and out the tapered distal end 17 thereof which is seated within the guidewire port 29 of the easily exchangeable dilatation catheter 27.
  • the replacement guidewire 21 may be positioned within the inner lumen 25 before the in-place guidewire 28 is removed.
  • the advancement of the replacement guidewire 21 continues until the distal tip thereof extends out the distal end of the dilatation catheter 27 into the patient's coronary artery.
  • the exchange device may then be removed from the patient.
  • the guidewire exchange device As the guidewire exchange device is withdrawn from the patient, it is stripped from the replacement guidewire 21 through slits 20 and 22 in the proximal section 11 as shown in FIG. 14.
  • the guidewire exchange device When the guidewire exchange device is withdrawn completely from the patient so that the replacement guidewire 21 extends out the proximal port 14 and bare guidewire 21 is visible extending out the distal end 17 of the exchange device, the exposed guidewire distal to the distal end 17 can be manually grasped to hold the guidewire in position while the exchange device is removed therefrom.
  • the readily exchangeable dilatation catheter 27 can be exchanged for another readily exchangeable dilatation catheter over either the in-place guidewire 28 or the replacement guidewire 21.
  • the overall length of the guidewire exchange device is typically about 85 to about 130 cm.
  • the transverse dimensions are for the most part controlled by the maximum transverse dimension of the guidewires to be used but they generally range from about 0.03 to about 0.05 inch (0.76-1.3 mm) in outer diameter.
  • the length of the distal section can range from about 1 to about 40 cm, but preferably ranges from about 7 to about 20 cm.
  • the hypotubing of the proximal section 11 can be formed of stainless steel or a superelastic NiTi alloy and the jacket can be a low density polyethylene.
  • the distal section 12 and the sleeve 13 may be formed of a high density polyethylene.
  • the guiding catheter, the dilatation catheter and the guidewires can be of conventional construction and materials.

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Claims (11)

  1. Dispositif d'échange de fil de guidage intravasculaire (10), comprenant une tige allongée, ladite tige incluant des sections proximale et distale de tige et l'extrémité distale de ladite section distale de tige est conçue pour faire saillie dans un orifice de fil de guidage d'un cathéter, caractérisé en ce que :
    la section distale de tige (12) comprend un manchon extérieur (13) au niveau de la jonction avec la section proximale de tige et possède au moins une partie distale de cette dernière configurée pour être avancée dans une artère coronaire d'un patient et dans un orifice de fil de guidage proximal (29) d'un cathéter intravasculaire du type à échange rapide (27), un premier orifice de fil de guidage dans l'extrémité distale (17) de ladite section distale de tige (12), un deuxième orifice de fil de guidage (14) dans l'extrémité proximale de ladite section de tige distale (12), et un premier passage intérieur ouvert de réception de fil de guidage (15) qui est disposé à l'intérieur de ladite section distale de tige et s'étendant depuis le premier orifice de fil de guidage dans l'extrémité distale de cette dernière (17) jusqu'au deuxième orifice de fil de guidage (14) ; et
    ladite section proximale de tige (11) ayant une longueur supérieure à ladite section distale de tige et l'extrémité distale de la section proximale de tige (11) étant solidement fixée à la section distale de tige au niveau d'un emplacement entre les premier et deuxième orifices de fil de guidage (17, 14), un troisième orifice de fil de guidage dans l'extrémité distale de ladite section proximale de tige et ledit troisième orifice de fil de guidage est situé entre les premier et deuxième orifices de fil de guidage et est en communication de fluide avec le premier passage intérieur de réception de fil de guidage (15), un quatrième orifice de fil de guidage dans l'extrémité proximale de ladite section proximale de tige (11), et un second passage intérieur ouvert de réception de fil de guidage (25) qui est disposé à l'intérieur de la section proximale de tige et, s'étendant entre les troisième et quatrième orifices de fil de guidage, communique avec le premier passage de réception de fil de guidage (15) dans la section distale de tige (12) à travers le troisième orifice de fil de guidage dans l'extrémité distale de la section proximale de tige, et ledit second passage intérieur de réception de fil de guidage (25) coupant le premier passage intérieur de réception de fil de guidage (15) à un angle aigu.
  2. Dispositif d'échange de fil de guidage intravasculaire selon la revendication 1, dans lequel le deuxième orifice de fil de guidage (14) dans la section distale de tige est espacé de manière proximale d'au moins environ 1 cm du premier orifice de fil de guidage (17) de la section distale de tige.
  3. Dispositif d'échange de fil de guidage intravasculaire selon la revendication 1, dans lequel une partie distale de la section proximale de tige (11) est orientée à un certain angle par rapport à une partie proximale de la section distale de tige (12).
  4. Dispositif d'échange de fil de guidage intravasculaire selon la revendication 1, dans lequel une partie distale de la section proximale de tige (11) est décalée par rapport à une partie proximale de la section distale de tige (12).
  5. Ensemble d'échange de fil de guidage intravasculaire comprenant le dispositif d'échange de fil de guidage intravasculaire de la revendication 1 et un fil de guidage (21, 28) disposé de manière coulissante, l'un des passages intérieurs de réception de fil de guidage (25, 15) étant à l'intérieur de la section proximale ou distale de tige (11, 12).
  6. Ensemble d'échange de fil de guidage intravasculaire selon la revendication 5, dans lequel une partie distale de la section proximale de tige (11) du dispositif d'échange intravasculaire est orientée à un certain angle par rapport à une partie proximale de la section distale de tige (12).
  7. Ensemble d'échange de fil de guidage intravasculaire selon la revendication 5, dans lequel une partie distale de la section proximale de tige (11) du dispositif d'échange intravasculaire est décalée par rapport à une partie proximale de la section distale de tige (12).
  8. Ensemble intravasculaire, comprenant :
       un cathéter intravasculaire du type à échange rapide (27) ayant une tige allongée qui est configurée pour une introduction percutanée et pour avancer à l'intérieur de la vasculature d'un patient humain jusqu'à une artère coronaire de cette dernière, ladite tige incluant une section distale de tige souple qui comporte au moins une partie distale de cette dernière configurée pour être avancée à travers l'artère coronaire du patient, un premier orifice de fil de guidage dans l'extrémité distale de la tige de cathéter et un deuxième orifice de fil de guidage (29) dans la tige de cathéter espacé de façon proximale de l'extrémité distale de la tige de cathéter, un passage de réception de fil de guidage (30) s'étendant à l'intérieur de la partie distale de la tige de cathéter entre les deux orifices de fil de guidage ; et le dispositif d'échange de fil de guidage intravasculaire de la revendication 1.
  9. Ensemble intravasculaire selon la revendication 8 incluant un fil de guidage (21) disposé de façon coulissante au moins à l'intérieur du second passage intérieur de réception de fil de guidage (25) à l'intérieur de la section proximale de tige (11) du dispositif d'échange de fil de guidage (10).
  10. Ensemble intravasculaire selon la revendication 8, dans lequel une partie distale de la section proximale de tige (11) du dispositif d'échange de fil de guidage (10) est orientée à un certain angle par rapport à une partie proximale de la section distale de tige (12).
  11. Ensemble intravasculaire selon la revendication 8, dans lequel une partie distale de la section proximale de tige (11) du dispositif d'échange de fil de guidage (10) est décalée par rapport à une partie proximale de la section distale de tige (12).
EP93904480A 1992-01-09 1993-01-08 Dispositif de remplacement de fil de guidage Expired - Lifetime EP0620750B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US81828892A 1992-01-09 1992-01-09
US818288 1992-01-09
PCT/US1993/000067 WO1993013827A1 (fr) 1992-01-09 1993-01-08 Dispositif de remplacement de fil de guidage

Publications (3)

Publication Number Publication Date
EP0620750A1 EP0620750A1 (fr) 1994-10-26
EP0620750A4 EP0620750A4 (fr) 1995-04-26
EP0620750B1 true EP0620750B1 (fr) 2001-04-11

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EP93904480A Expired - Lifetime EP0620750B1 (fr) 1992-01-09 1993-01-08 Dispositif de remplacement de fil de guidage

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US (5) US5571094A (fr)
EP (1) EP0620750B1 (fr)
JP (1) JPH07509379A (fr)
AT (1) ATE200432T1 (fr)
CA (1) CA2117386A1 (fr)
DE (1) DE69330119T2 (fr)
WO (1) WO1993013827A1 (fr)

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US5984945A (en) 1999-11-16
CA2117386A1 (fr) 1993-07-22
DE69330119T2 (de) 2001-08-02
WO1993013827A1 (fr) 1993-07-22
US5571094A (en) 1996-11-05
US20030093039A1 (en) 2003-05-15
EP0620750A1 (fr) 1994-10-26
ATE200432T1 (de) 2001-04-15
DE69330119D1 (de) 2001-05-17
EP0620750A4 (fr) 1995-04-26
US5919175A (en) 1999-07-06
JPH07509379A (ja) 1995-10-19
US6524285B1 (en) 2003-02-25

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